Kryspin Andrzejewski, Agnieszka Wrzesień, Małgorzata Zaremba, Ilona Joniec-Maciejak, Silvia V Conde, Katarzyna Kaczyńska
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We also investigated the effects of supplementation with the DA biosynthesis precursor L-DOPA on HVR and central DA depletion on hypoxic phrenic (PHR) and hypoglossal (HG) nerve activity.</p><p><strong>Methods: </strong>After 6-OHDA intrastriatal injection, awake Wistar rats were tested in a plethysmographic chamber to study the HVR (8% O<sub>2</sub>) before and after L-DOPA treatment. Registration of PHR and HG under acute hypoxia (8% O<sub>2</sub>) was performed in anesthetized rats.</p><p><strong>Results: </strong>The 6-OHDA rats showed reduced normoxic ventilation and HVR, eliminated by L-DOPA treatment. Increased HG activity during hypoxia in the form of increased amplitude and pre-inspiratory amplitude was observed. In addition to decreased striatal levels of DA, serotonin (5-HT) and noradrenaline (NA), reduced NA (42%) and 5-HT (52%) were found in CB of 6-OHDA rats. The open-field test showed a decrease in motor activity 2 weeks after the lesion.</p><p><strong>Conclusions: </strong>Our results showed NA and 5-HT deficits in CB in the PD model, which may be responsible for impaired HVR. L-DOPA treatment, replenishing DA deficiency in the striatum, stimulated HVR. Increased pre-inspiratory HG activity indicates modifications to the central mechanisms controlling their activity.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 4","pages":"e70035"},"PeriodicalIF":5.2000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impaired Breathing During Exposure to Hypoxia and Carotid Body Dysfunction in an Animal Model of Parkinson's Disease.\",\"authors\":\"Kryspin Andrzejewski, Agnieszka Wrzesień, Małgorzata Zaremba, Ilona Joniec-Maciejak, Silvia V Conde, Katarzyna Kaczyńska\",\"doi\":\"10.1002/cph4.70035\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Parkinson's disease (PD) manifestations involve respiratory dysfunction and motor disability. Previous research on PD has mainly focused on central dopamine (DA) deficits and their effect on ventilation.</p><p><strong>Objectives: </strong>The purpose of the study was to analyze the function of carotid bodies (CB), sensors of blood O<sub>2</sub>, by studying the hypoxic ventilatory response (HVR) and measuring biogenic amine content in the CB of a 6-hydroxydopamine (6-OHDA) induced PD model. We also investigated the effects of supplementation with the DA biosynthesis precursor L-DOPA on HVR and central DA depletion on hypoxic phrenic (PHR) and hypoglossal (HG) nerve activity.</p><p><strong>Methods: </strong>After 6-OHDA intrastriatal injection, awake Wistar rats were tested in a plethysmographic chamber to study the HVR (8% O<sub>2</sub>) before and after L-DOPA treatment. Registration of PHR and HG under acute hypoxia (8% O<sub>2</sub>) was performed in anesthetized rats.</p><p><strong>Results: </strong>The 6-OHDA rats showed reduced normoxic ventilation and HVR, eliminated by L-DOPA treatment. Increased HG activity during hypoxia in the form of increased amplitude and pre-inspiratory amplitude was observed. In addition to decreased striatal levels of DA, serotonin (5-HT) and noradrenaline (NA), reduced NA (42%) and 5-HT (52%) were found in CB of 6-OHDA rats. The open-field test showed a decrease in motor activity 2 weeks after the lesion.</p><p><strong>Conclusions: </strong>Our results showed NA and 5-HT deficits in CB in the PD model, which may be responsible for impaired HVR. L-DOPA treatment, replenishing DA deficiency in the striatum, stimulated HVR. 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Impaired Breathing During Exposure to Hypoxia and Carotid Body Dysfunction in an Animal Model of Parkinson's Disease.
Background: Parkinson's disease (PD) manifestations involve respiratory dysfunction and motor disability. Previous research on PD has mainly focused on central dopamine (DA) deficits and their effect on ventilation.
Objectives: The purpose of the study was to analyze the function of carotid bodies (CB), sensors of blood O2, by studying the hypoxic ventilatory response (HVR) and measuring biogenic amine content in the CB of a 6-hydroxydopamine (6-OHDA) induced PD model. We also investigated the effects of supplementation with the DA biosynthesis precursor L-DOPA on HVR and central DA depletion on hypoxic phrenic (PHR) and hypoglossal (HG) nerve activity.
Methods: After 6-OHDA intrastriatal injection, awake Wistar rats were tested in a plethysmographic chamber to study the HVR (8% O2) before and after L-DOPA treatment. Registration of PHR and HG under acute hypoxia (8% O2) was performed in anesthetized rats.
Results: The 6-OHDA rats showed reduced normoxic ventilation and HVR, eliminated by L-DOPA treatment. Increased HG activity during hypoxia in the form of increased amplitude and pre-inspiratory amplitude was observed. In addition to decreased striatal levels of DA, serotonin (5-HT) and noradrenaline (NA), reduced NA (42%) and 5-HT (52%) were found in CB of 6-OHDA rats. The open-field test showed a decrease in motor activity 2 weeks after the lesion.
Conclusions: Our results showed NA and 5-HT deficits in CB in the PD model, which may be responsible for impaired HVR. L-DOPA treatment, replenishing DA deficiency in the striatum, stimulated HVR. Increased pre-inspiratory HG activity indicates modifications to the central mechanisms controlling their activity.
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Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered.
This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
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